This Exploratory/Developmental Research Funding
Opportunity intends to support gene function studies in collaboration with
the Undiagnosed Diseases Network (UDN) building upon the NIH Intramural
Research Program’s Undiagnosed Diseases Program (NIH-UDP). Responsive
applications will propose to investigate the underlying genetics,
biochemistry and/or pathophysiology of newly diagnosed diseases in
association with the respective gene variant(s) identified through the UDN.
In recent years, gene function studies combined with genetic and genomic
analyses and metabolic studies have greatly improved diagnoses of these very
rare diseases and advanced scientific knowledge of the underlying
pathogenesis. This initiative is funded through the NIH Common Fund, which
supports cross-cutting programs that are expected to have exceptionally high
impact.

Key Dates

Posted Date

April 18, 2014

Open Date (Earliest Submission Date)

May 23, 2014

Letter of Intent Due Date(s)

May 23, 2014

Application Due Date(s)

June 23, 2014, by 5:00 PM local time of applicant
organization.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

October/November, 2014

Advisory Council Review

January, 2015

Earliest Start Date

April, 2015

Expiration Date

June 24, 2014

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA)
is required and strictly enforced. Applicants must read and follow all
application instructions in the Application Guide as well as any
program-specific instructions noted in Section
IV. When the program-specific instructions deviate from those in the
Application Guide, follow the program-specific instructions. Applications that
do not comply with these instructions may be delayed or not accepted for review.

This initiative is funded through
the NIH Common Fund, which supports cross-cutting programs that are expected to
have exceptionally high impact. All Common Fund initiatives invite
investigators to develop bold, innovative, and often risky approaches to
address problems that may seem intractable or to seize new opportunities that
offer the potential for rapid progress.

Nature of the Research Opportunity

The purpose of this Funding Opportunity Announcement (FOA)
is to support gene function studies in collaboration with the NIH Intramural Undiagnosed
Diseases Program (NIH-UDP) to investigate the underlying genetics, biochemistry
and pathophysiology of newly diagnosed diseases (Diseases of Interest) in
association with the respective gene variant(s) identified through the NIH-UDP.

Background

Over the past decade, the NIH Office of Rare Diseases
Research (ORDR, NCATS) has received thousands
of inquiries regarding patients’ undiagnosed diseases. Of those individuals
seeking assistance, 6% were found to have an undiagnosed disorder. The NIH-UDP
began in May 2008 and has received approximately 9,000 inquiries over a five-year
period. From these inquiries, the investigators were able to evaluate 3,000
medical records and admit 650 patients to the NIH Clinical Center for thorough,
one-week evaluations. The NIH-UDP discovered and described two unknown diseases
and identified dozens of genes not previously associated with human disease. While
the ability to diagnose these rare and yet to be described diseases has been
revolutionized by the use of genomic analyses, it is gene function studies that
uncover the links among gene defects, patient phenotypes, and diseases.

Building on the success of the NIH-UDP, the NIH is
developing the existing UDP into a larger program, the Undiagnosed Disease
Network (UDN), with a commitment to the advancement of diagnosis of rare
diseases. This commitment includes the expansion of the UDP into a network of
clinical sites containing the NIH Intramural Research Program, extramural UDN
Clinical Sites, a Coordinating Center and a number of Core Laboratory Services
that may change as the science and needs of the program evolve.

Scientific Knowledge to be Achieved

UDP patients present compelling research questions since
clarification of the underlying genetics, biochemistry, cell biology and physiology
of these disorders will lead to a better understanding of their disease
processes and those of related disorders. Investigation of function of the
suspected abnormal allele is a critical step in the process leading to
diagnosis and potential treatment of patients with these rare diseases. These
studies provide the causal link between the genetic defects and patient
phenotypes. Over half of the UDP newly diagnosed diseases (Diseases of
Interest) involve neurological dysfunction or developmental delay; the
remaining phenotypes span metabolic, skeletal and inflammatory disease among
others. A current list of UDP Diseases of Interest and the associated gene
variant(s) linked to these diseases is provided on the UDN website (http://www.genome.gov/27551936).

Scientific Scope

Applications may employ a wide variety of investigative
approaches to explore the specific genes and phenotypes listed in the UDN
website (http://www.genome.gov/27551936). Applicants are expected to conduct
integrated studies of individual genes or gene networks in the relevant physiological/pathophysiological
environment across any of several levels including molecular, cell, tissue,
organ, and model organisms. Before submitting an application, investigators are
strongly encouraged to review the specific detailed information available on
the UDN website (http://www.genome.gov/27551936) about each gene, variant and
associated human phenotype. If necessary, applicants may contact the UDN
website (http://www.genome.gov/27551936) to ask questions about the gene variant, its
validation and associated clinical phenotype of the disease of interest. In
addition, applicants can inquire about the availability of patient
bio-specimens and other available resources for gene function studies.

The goal of this FOA is to obtain mechanistic understanding
of (1) whether and how the genetic variation affects gene expression and
function particularly as it relates to the disease phenotype, and (2) whether
and how particular genes and their specific variants are involved in the
disease pathogenesis. Several of the genes on the list may have
pleiotropic functions or function in known pathways that may or may not be
relevant to the newly diagnosed disease of interest. Applicants should utilize
bioinformatics approaches or literature searches to provide a rationale to
substantiate the link between the gene variant, the proposed genetic mechanism
(i.e. gain of function or loss of function), and the phenotype. Applicants
should also explain their approach to exploring the gene variant(s) and how
this approach synergizes with the patient and family information available.
Highest priority will be given to those applications that can provide new
mechanistic insight into the function of a specific gene or gene network
implicated in a specific phenotype seen in a patient(s) in the UDP.

This announcement is not meant to support the development of
broad screening tests in model organisms for undiagnosed disease patients.

Examples of research may include, but are not limited to:

Use of model organisms (including mice, flies, zebrafish, worms,
and yeast) to assess the contribution of the gene variant to the genetic
mechanism (i.e. loss of function versus gain of function), disease etiology,
pathophysiology and phenotype.

Examination of spatiotemporal expression patterns of the genes
and their protein products, their upstream and downstream regulation, protein
interactions and signaling partners to understand the potential contribution of
the gene variants to the respective Diseases of Interest.

Exploration of the contribution of the disease-related gene
variants to abnormalities in gene expression or function in patient
bio-specimens.

Investigators interested in applying to this FOA should go
to the UDN website (http://www.genome.gov/27551936) where they will find a list of
gene variants of interest to the UDN and contact information to link potential
applicants with the investigators of the UDP to discuss scientific and
technical issues prior to submission of an application.

Program Formation and Governance

The awards funded under this FOA will be exploratory/developmental.

Gene function research often requires building investigative
teams that cross scientific and clinical disciplines. UDN productivity will
depend on investigator collaboration in sharing of research plans; identifying
commonalities in approaches, barriers, and solutions; and developing common
resources such as educational, reporting, and evaluative tools. Shortly after
award, the Gene Function awardees will be introduced to other UDN investigators
in the network through the UDN Coordinating Center and will be encouraged to
participate in network meetings, such as steering committee meetings, to share
in the development of new strategies to address the common network goals.
Awardees will be able to learn about the clinical methods and technology
applied and in turn they will share their approaches and progress in defining
the functions of the specific genes of interest to the network. Through this
collaboration the Network will provide improvements in both the diagnosis and
treatment of rare diseases.

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or
both to an eligible entity to carry out an approved project or activity.

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number and SAM registration in order to complete the
eRA Commons registration. Organizations can register with the eRA Commons as
they are working through their SAM or Grants.gov registration. eRA Commons
requires organizations to identify at least one Signing Official (SO) and at
least one Program Director/Principal Investigator (PD/PI) account in order to
submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.
PD(s)/PI(s) should work with their organizational officials to either
create a new account or to affiliate their existing account with the applicant
organization in eRA Commons. If the PD/PI is also the organizational Signing Official,
they must have two distinct eRA Commons accounts, one for each role. Obtaining
an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the
same as one already reviewed within the past thirty-seven months (as described
in the NIH
Grants Policy Statement), except for submission:

To an RFA of an application that was submitted previously as an
investigator-initiated application but not paid;

Of an investigator-initiated application that was originally
submitted to an RFA but not paid; or

Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1.
Overview Information, prospective applicants are asked to submit a letter
of intent that includes the following information:

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

Required and Optional Components

The forms package associated with this FOA includes all
applicable components, required and optional. Please note that some components
marked optional in the application package are required for submission of
applications for this FOA. Follow all instructions in the SF424 (R&R)
Application Guide to ensure you complete all appropriate “optional” components.

Instructions for Application Submission

The following section supplements the instructions found in
the SF424 (R&R) Application Guide and should be used for preparing an
application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must
be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Specific
Aims: List each aim for this application and how it supports
the Objectives of this Research Program as described in Section I. Funding Opportunity Description.

Research
Strategy: In describing the research strategy, list the
investigative approaches. Applicants are expected to conduct integrated studies
of individual genes or gene networks in the relevant
physiological/pathophysiological environment across any of several levels
including molecular, cell, tissue, organ, and model organisms.

Applicants should utilize bioinformatics approaches or
literature searches to provide a rationale to substantiate the link between the
gene variant, the proposed genetic mechanism (i.e. gain of function or loss of
function), and the phenotype. Applicants should also explain their approach to
exploring the gene variant(s) and how this approach synergizes with the patient
and family information available.

Resource
Sharing Plan: Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424
(R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs
requested for any one year, should address a Data Sharing Plan.

Data from the UDN are expected to be handled so as to increase
the value of the significant public investment in the creation and operation of
the Network. Consistent with achieving the goals of the UDN program, the data
sharing plan should describe how final research information such as protocols,
methods, biological results, descriptions, bioinformatics tools, and
publications will be shared among the UDN, made available through an open
access section of a database such as dbGAP, other public websites, as well as
with the research community at large. Any barriers to achieving such data
sharing should be addressed. For additional information on the NIH Data Sharing
Policy, see http://grants.nih.gov/grants/policy/data_sharing/.

The NIH also expects the timely sharing of biomedical resources
by grant recipients. The resources sharing plan should also describe how unique
research resources will be distributed, e.g., through the institution, a
repository, or national coordinating center. For information regarding research
resources sharing, see http://grants.nih.gov/grants/sharing.htm.
Information regarding the sharing of model organisms can be found at http://grants.nih.gov/grants/policy/model_organism/.

Appendix:
Do not use the Appendix to circumvent page limits. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

Planned Enrollment Report

When conducting clinical research, follow all instructions
for completing Planned Enrollment Reports as described in the SF424 (R&R)
Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions
for completing Cumulative Inclusion Enrollment Report
as described in the SF424 (R&R) Application Guide.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies
described in the NIH Grants
Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications
before the due date to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date. If a Changed/Corrected application is submitted after the deadline,
the application will be considered late.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the System for Award Management. Additional information may be
found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review and responsiveness by
components of participating organizations, NIH. Applications that are
incomplete and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to
notify the NHGRI Referral Office by email at nakamurk@mail.nih.gov when the
application has been submitted. Please include the FOA number and title, PD/PI
name, and title of the application.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

For this particular announcement, note the following:

This FOA supports investigations of the underlying genetics,
biochemistry and pathophysiology of newly diagnosed diseases (Diseases of
Interest) in association with the respective gene variant(s) identified through
the NIH-UDP. These studies may include novel scientific ideas or new model
systems, tools, or technologies that have the potential for significant impact
on understanding the genetic mechanism or pathology underlying individuals seen
at the NIH-UDP. An R21 grant application need not have extensive background
material or preliminary information.

Accordingly, reviewers should note that this announcement is not
meant to support the development of broad screening tests in model organisms
for undiagnosed disease patients.

Reviewers should focus on whether applicants have utilized
bioinformatics approaches or literature searches to provide a rationale to
substantiate the link between the gene variant, the proposed genetic mechanism
(i.e. gain of function or loss of function), and the phenotype of the
individual associated with the gene listed in the UDN website. Appropriate
justification of the proposed approach to exploring the gene variant(s) and
how this approach synergizes with the patient and family information available
can be provided through literature citations, data from other sources, or, when
available, from investigator-generated data.

Reviewers should focus their evaluation on the conceptual
framework, the level of innovation, and the potential to significantly advance
our knowledge or understanding of mechanistic insight into the function of a
specific gene or gene network and its link to a specific phenotype seen in a
patient(s) in the UDP. Preliminary data are not required for R21 applications;
however, they may be included if available.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD/PI, do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be
managed? Does the project provide adequate depth in the proposed mechanistic
studies to validate or invalidate a causal link between the gene variant(s) and
the disease(s)?

If the project involves human subjects and/or NIH-defined clinical research,
are the plans to address 1) the protection of human subjects from research
risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender,
race, and ethnicity, as well as the inclusion or exclusion of children,
justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Guidelines
for the Review of Human Subjects.

Inclusion of Women, Minorities, and
Children

When the proposed project involves human subjects
and/or NIH-defined clinical research, the committee will evaluate the proposed
plans for the inclusion (or exclusion) of individuals on the basis of
sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of
children to determine if it is justified in terms of the scientific goals and
research strategy proposed. For additional information on review of the
Inclusion section, please refer to the Guidelines
for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the
application as now presented, taking into consideration the responses to
comments from the previous scientific review group and changes made to the
project.

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the National
Institute of Human Genome Research, in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in
response to this FOA.

Applications will be assigned on the basis of established
PHS referral guidelines to the appropriate NIH Institute or Center. Applications
will compete for available funds with all other recommended applications submitted
in response to this FOA. Following initial peer review, recommended applications
will receive a second level of review by the appropriate national Advisory
Council or Board. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

When multiple years are involved, awardees will be required
to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR)
and financial statements as required in the NIH Grants
Policy Statement.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants
Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and
405 of the Public Health Service Act as amended (42 USC 241 and 284) and under
Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.